Collagen is the major insoluble fibrous protein in the extracellular matrix and in connective tissue. There are at least nineteen types of collagen, but 80% to 90% of the collagen in the body is composed of the conventional well-known Type I, Type II, and Type III forms. The collagen molecule is a triple helix, each helical coil a biological polypeptide polymer constructed from glycine (C2H5NO2), alanine (C3H7NO2), proline (C5H9NO2), and hydroproline (C5H9NO3). As the three helices wrap around each other, hydrogen bonds form between each helix to maintain the structure. Collagen molecules pack together to form long, thin fibrils. The most prominent collagen types are:    Type I. The primary component of tendons, ligaments, and bones.    Type II. The primary protein constituent (more than 50%) in cartilage.    Type III. Strengthens the walls of hollow structures like arteries, the intestine, and the uterus.    Type IV. Forms the basal lamina (also called the basement membrane) of epithelia.
As a support structure, collagen fibrils are found in many environments within the body. The strength and relative elasticity of the collagen structure allow tendon and ligament structures to function in their role which requires great strength to manipulate skeletal structures. Up to 90% of the dry weight of tendons is collagen (at least 30% of the total weight), up to 50% of the dry weight of articular cartilage and synovial tissue is collagen (5% to 30% of total weight). Collagen comprises 75% of the dry weight of skin.
The helical structure and the nature of the hydrogen bond cross-linking of the collagen molecule cause it to react when heated. The cross-linking bonds break and the helix, which is a type of spring structure, collapses somewhat. The result is a shrinkage, not unlike the process which occurs when a woolen garment is washed in hot water and heated in a dryer. The amount of shrinkage is a function of time and temperature [see FIG. 1] and is well known.
Several therapeutic remedies have been developed which utilize the thermal response of collagen to affect shrinkage and/or for treating disease and, thereby, therapy. Among these are capsulorrhaphy, or the shrinkage of the tendon and capsular properties of the joints, shrinkage of the endopelvic fascia to address urinary incontinence, shrinkage of the bladder neck to affect treatment for urinary incontinence, shrinkage of sub-epidermal collagen for producing tightening of tissue to affect cosmetic outcomes, thermal treatment of benign and malignant tumors, among others.
A limitation of procedures for collagen shrinkage, however, is that the cell necrosis accompanying those procedures [see FIG. 1] weakens the structural integrity of the fibrils. It is known that shrinking capsular tissue more than 20% will weaken a structure so much that it will distort more under normal forces than it would if there had been no shrinkage at all [see FIG. 2]. Treatment of tumors usually involves delivering a thermal dose that guarantees cell necrosis, thus significantly changing collagen structure.
Thermally-induced shrinkage procedures have been received with moderate success because they have often produced variable results. Collagen shrinkage is a function of both time and temperature, but relatively small variations in either time or temperature can have dramatic results on the level of shrinkage [see FIG. 3]. Structures experiencing overshrinkage are likely to have limited, or adverse results. Structures with insufficient shrinkage are likely to have limited results.
Some therapy systems measure tissue temperature during treatment using invasive probes and predict associated tissue modification, while others estimate the temperature based on power-time-temperature parametric curves established from imperical measurements. But, because thermal dose, and thus collagen shrinkage, is an integral function of both time and temperature in combination with spatial distribution, and since slight variations in temperature during a specific time period can cause dramatic changes in collagen shrinkage [see FIG. 3], temperature measurement alone is not truly sufficient. In response to the need to effectively determine dosage of the thermal treatment, a noninvasive measure of the thermal dose or its affects, including collagen changes, is badly needed.
Since optimizing collagen modification, including shrinkage, is the goal of specific procedures, what is needed is a system and method for directly measuring the shrinkage of the collagen structure, rather than temperature. A system and method which could monitor tissue properties concurrent with treatment, signaling the operator to halt thermal application when collagen shrinkage approaches 20% could produce greatly improved results [see FIG. 3], reducing the inconsistency associated with the thermal shrinkage procedures.
The limitations of the previous art for monitoring tissue treatment resulting from thermal injury are inadequate to provide information directly related to collagen changes sufficient to provide optimal control of extent of collagen structural modification, including shrinkage.
It has been demonstrated that changes in collagen content of tissue affects certain acoustic properties, namely the speed of sound in that tissue structure and the absorption of the acoustic energy as it passes through that tissue [see FIG. 4A]. It has been shown in the art that there is a linear function of both acoustic velocity and acoustic attenuation (see FIG. 4B) with variations in collagen content. Acoustic velocity changes 5 m/sec/(% change in collagen concentration) and acoustic attenuation changes 0.666 db/m/(% change in collagen concentration).
As an example, a 20% shrinkage in a collagen structure having an initial collagen content of 30% should cause a 25% increase in the % collagen by weight of the tissue structure. Since many collagen structures are 5% to 30% collagen (by weight), a 25% increase in density due to therapeutic shrinkage would cause a change in collagen content of 1.25% to 7.5%. These changes would correspond to changes in acoustic velocity of 6.25 m/sec to 37.5 m/sec, for initial collagen contents of 5% and 30%, respectively (see FIG. 5A). These changes would correspond to changes in acoustic attenuation of 0.833 db/m to 5 db/m, respectively [see FIG. 5B].
In addition to changes in acoustic velocity and attenuation, the structural patterns of the tissue change permanently as a function of thermally-induced necrosis and density changes. These patterns may be characterized in an analysis of the structures in the 2D or 3D acoustic image or in 2D spatial maps of acoustic signals that are reflected from or transmitted through the tissue in those locations. Applying pattern recognition methods and/or expert system techniques to the backscatter image or signal mapping data can yield useful information in addition to attenuation and velocity measurements alone.
Ultrasound (acoustic) imaging has been used in medical imaging for years to differentiate tissue structures. These imaging techniques have examined acoustic properties of ultrasound waves as they travel through and reflect off of tissue to distinguish tissue types and the boundaries between those types. These devices map tissue in two dimensions (along a plane in line with an imaging transducer) or three dimensions (by using multi-element imaging transducers or single-line imaging transducers whose focus or location changes during the process. Two of the acoustic properties used in these imaging techniques are acoustic velocity and acoustic attenuation. Further, structural change analyses using pattern recognition methods can provide an ability to track changes in tissue structure/collagen structure from baseline using backscattered image information.
The ability to map those changes in tissue and assign changes in collagen density to the mapped functions would allow users the ability to monitor, in real time, the therapy effect they are seeking to accomplish.